A bio-artificial pancreas, which will be designated hereafter by the abbreviation PBA, is more effective when its response to a concentration variation of the glucose in the blood is closer to that of the biological pancreas. Insulin must be secreted by the islets and reach the blood stream before the glycemia reaches an acceptable maximum, however much the slope of the curve of glycemia increase differs from the normal rate.
Numerous studies have already been made for providing a PBA having acceptable kinetics. A summary of these studies may be found in a paper by G. REACH et al in "Journees Annuelles de Diabetologie de l'Hotel-Dieu", Flammarion, Paris, 1982, pp 147 to 159.
In all devices, the operating principle is the same: the islets of Langerhans are separated from the diabetic host by an artificial bio-compatible membrane permeable to glucose and insulin. Two types of transfer of the glucose to the islets of Langerhans causing excitation of the latter have been proposed which lead to membranes of two different natures.
A first type of membrane uses diffusion, i.e. the passage of the liquid solution through the membrane. This amounts to dialysis, which is not satisfactory, for it requires a concentration gradient, which delays the stimulation of the islets of Langerhans and takes place at different speeds for glucose and insulin. This has a detrimental effect on the transfer function of the regulation process between the glycemic variations and the delivery of insulin into the blood.
Another type of membrane operates mainly due to convection--also known as ultrafiltration--i.e. the passage through the membrane of the solvent which takes with it the substances dissolved therein. Ultrafiltration membranes are usable for this type of transfer; they retain the heaviest molecules. No concentration gradient is required, which is a favorable factor, and the transfer speed is determined by the hydrostatic pressure gradient through the membrane and its hydraulic permeablility.
Attempts have already been made to construct a PBA using a ultrafiltration membrane. A PBA is known (U.S. Pat. No. 4,242,460 to Chick et al.) in which the cells are disposed between the jointing turns of helices through which the blood flows in reverse directions and contained in a cylindrical case. With this double helix arrangement only a small fraction of the filtering membranes in the form of a helix is used (that which borders the narrow canals defined by two adjacent turns) and the convective current only flows through a small part of the volume in which the islets are placed. The islets which are not in this part remain unused.
Moreover, some PBAs which have a satisfactory response when a sudden increase of the glycemia occurs (obtained for example during tests by intravenous injection) do not allow the glycemia to be maintained below the tolerable limit in the case of a slow variation, e.g. following a meal.
It is an object of the invention to overcome that drawback and to provide a PBA which has (1) an improved response and allows the glycemia to be held at an acceptable rate whatever its law of variations in time; (2) uses the major part of the filtering area and most of the islets used; and (3) allows the arterial pressure alone to be used for the production of the ultrafiltrate, to the exclusion of any exogenous pump.
This result has been reached because of a fundamental approach to the phenomena which come into play, an approach which has led to the discovery that an essential parameter for determining the functional characteristics is the volume of the compartment containing the islands. Taking this analysis into account, the invention proposes a PBA comprising islands of Langerhans contained in a volume defined by two approximately parallel ultrafiltrating walls-which will be designated hereafter by the term "membranes" whose surfaces opposite the volume occupied by the islands are successively swept by the same blood stream over a length greater by at least one order of size than the distance which separates the membranes.
Such a PBA, where the islands occupy a flat volume, may be constructed with membranes of very different natures. Flat membranes may in particular be used, made for example from polyacrylonitrile such as the ones sold under the reference "AN 69" by RHONE POULENC. A web of hollow ultrafiltrating fibers may also be used. The geometric arrangements adoptable are also very diverse, as will be seen further on.
In practice, the volume V.sub.i occupied by the islands of Langerhans and defined by the membranes will comply with the condition: EQU V.sub.i =S.multidot.P.sub.M .multidot..tau..DELTA.P/8
in which:
.tau. is the acceptable time constant, and physiological studies thereof carried out on man indicate that it should not exceed 20 minutes and should, preferably, be 15 minutes at most; PA1 .DELTA.P is the available drive pressure difference, of the order of 80 mm of mercury in the general case of an ateriovenous shunt implant; PA1 S is the total membrane area; PA1 P.sub.M is the hydraulic permeability of the membrane.
The invention will be better understood from the detailed description of particular embodiments.